There have been major changes in our understanding of choroidal diseases in the last decade owing to multiple retinal and choroidal imaging related advances. A major conceptual pivot is establishment of pachychoroid and its spectrum of clinical disorders: pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, peripapillary pachychoroid syndrome, and focal choroidal excavation. However, considerable overlaps in manifestations and therapeutics of these disorders make differentiation amongst them difficult. This review is focused on pathogenesis and clinical aspects of pachychoroid neovasculopathy (PNV). Since PNV was defined as a separate entity around 5 years ago, there have been numerous contrasting observations surrounding it. We review and summarize these studies, and also compare PNV with other disorders of the pachychoroid spectrum in detail. There are important differences between etiologies of neovascular age related macular degeneration and PNV. Yet the current treatment strategies for PNV have been extrapolated from the trials for the former. Future research needs to validate this assumption with long-term results.
PotsaidBBaumannBHuangD, et al. Ultrahigh speed 1050 nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second. Opt Express2010; 18: 20029–20048.
3.
ImamuraYFujiwaraTMargolisR, et al. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina2009; 29: 1469–1473.
FungATYannuzziLAFreundKB. Type 1 (sub-retinal pigment epithelial) neovascularization in central serous chorioretinopathy masquerading as neovascular age-related macular degeneration. Retina2012; 32: 1829–1837.
ArfSSayman MuslubasIHocaogluM, et al. Features of neovascularization in pachychoroid neovasculopathy compared with type 1 neovascular age-related macular degeneration on optical coherence tomography angiography. Jpn J Ophthalmol2020; 64: 257–264.
8.
JungBJKimJYLeeJH, et al. Intravitreal aflibercept and ranibizumab for pachychoroid neovasculopathy. Sci Rep2019; 9: 2055.
9.
MatsumotoHHiroeTMorimotoM, et al. Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration. Jpn J Ophthalmol2018; 62: 144–150.
10.
MiyakeMOotoSYamashiroK, et al. Pachychoroid neovasculopathy and age-related macular degeneration. Sci Rep2015; 5: 16204.
11.
CarnevaliACapuanoVSacconiR, et al. OCT angiography of treatment-naïve quiescent choroidal neovascularization in pachychoroid neovasculopathy. Ophthalmol Retina2017; 1: 328–332.
12.
Gallego-PinazoRDolz-MarcoRGómez-UllaF, et al. Pachychoroid diseases of the macula. Med Hypothesis Discov Innov Ophthalmol2014; 3: 111–115.
13.
SemeraroFMorescalchiFRussoA, et al. Central serous chorioretinopathy: pathogenesis and management. Clin Ophthalmol2019; 13: 2341–2352.
14.
KumarAKumawatDSundarM D, et al. Polypoidal choroidal vasculopathy: a comprehensive clinical update. Ther Adv Ophthalmol2019; 11: 2515841419831152.
15.
PhasukkijwatanaNFreundKBDolz-MarcoR, et al. Peripapillary pachychoroid syndrome. Retina2018; 38: 1652–1667.
16.
ChungHByeonSHFreundKB. Focal choroidal excavation and its association with pachychoroid spectrum disorders: a review of the literature and multimodal imaging findings. Retina2017; 37: 199–221.
17.
HuangDSwansonEALinCP, et al. Optical coherence tomography. Science1991; 254: 1178–1181.
18.
LiuBWangYLiT, et al. Correlation of subfoveal choroidal thickness with axial length, refractive error, and age in adult highly myopic eyes. BMC Ophthalmol2018; 18: 127.
19.
ZhaoMYangXFJiaoX, et al. The diurnal variation pattern of choroidal thickness in macular region of young healthy female individuals using spectral domain optical coherence tomography. Int J Ophthalmol2016; 9: 561–566.
20.
BayraktarSCebeciZIzgiB, et al. The effect of glaucoma medication on choroidal thickness measured with enhanced depth-imaging optical coherence tomography. Med Hypothesis Discov Innov Ophthalmol2019; 8: 44–51.
21.
IbrahimAMElgouharySMNassarMK, et al. Changes in choroidal thickness after cataract surgery. Semin Ophthalmol2018; 33: 664–670.
22.
ErsozMGKaracorluMArfS, et al. Outer nuclear layer thinning in pachychoroid pigment epitheliopathy. Retina2018; 38: 957–961.
23.
CheungCMGLeeWKKoizumiH, et al. Pachychoroid disease. Eye (Lond)2019; 33: 14–33.
24.
LehmannMBousquetEBeydounT, et al. Pachychoroid: an inherited condition?Retina2015; 35: 10–16.
25.
PrünteC. Indocyanine green angiographic findings in central serous chorioretinopathy. Int Ophthalmol1995; 19: 77–82.
26.
von WinningCHOosterhuisJARenger-van DijkAH, et al. Diffuse retinal pigment epitheliopathy. Ophthalmologica1982; 185: 7–14.
27.
MarukoIIidaTSuganoY, et al. Subfoveal choroidal thickness in fellow eyes of patients with central serous chorioretinopathy. Retina2011; 31: 1603–1608.
28.
SpaideRFCampeasLHaasA, et al. Central serous chorioretinopathy in younger and older adults. Ophthalmology1996; 103: 2070–2079; discussion 2079.
29.
LooRHScottIUFlynnHWJr, et al. Factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous chorioretinopathy. Retina2002; 22: 19–24.
30.
AzarGWolffBMauget-FaÿsseM, et al. Pachychoroid neovasculopathy: aspect on optical coherence tomography angiography. Acta Ophthalmol2017; 95: 421–427.
31.
DansinganiKKBalaratnasingamCKlufasMA, et al. Optical coherence tomography angiography of shallow irregular pigment epithelial detachments in pachychoroid spectrum disease. Am J Ophthalmol2015; 160: 1243–1254.e2.
32.
DansinganiKKBalaratnasingamCNaysanJ, et al. En face imaging of pachychoroid spectrum disorders with swept source optical coherence tomography. Retina2016; 36: 499–516.
33.
QuerquesGSrourMMassambaN, et al. Functional characterization and multimodal imaging of treatment-naive “quiescent” choroidal neovascularization. Investig Ophthalmol Vis Sci2013; 54: 6886–6892.
34.
GuptaMPRusuISeidmanC, et al. Pachychoroid neovasculopathy in extramacular choroidal neovascularization. Clin Ophthalmol2016; 10: 1275–1282.
35.
AkkayaS. Spectrum of pachychoroid diseases. Int Ophthalmol2018; 38: 2239–2246.
36.
CoscasGLupidiMCoscasF, et al. Toward a specific classification of polypoidal choroidal vasculopathy: idiopathic disease or subtype of age-related macular degeneration. Investig Ophthalmol Vis Sci2015; 56: 3187–3195.
37.
DansinganiKKGal-OrOSaddaSR, et al. Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of ‘expanded spectra’ – a review. Clin Exp Ophthalmol2018; 46: 189–200.
38.
EllabbanAATsujikawaAOotoS, et al. Focal choroidal excavation in eyes with central serous chorioretinopathy. Am J Ophthalmol2013; 156: 673–683.
39.
KonstantinidisLMantelIZografosL, et al. Intravitreal ranibizumab in the treatment of choroidal neovascularization associated with idiopathic central serous chorioretinopathy. Eur J Ophthalmol2010; 20: 955–958.
40.
PrünteCFlammerJ. Choroidal capillary and venous congestion in central serous chorioretinopathy. Am J Ophthalmol1996; 121: 26–34.
41.
CooperBAThomasMA. Submacular surgery to remove choroidal neovascularization associated with central serous chorioretinopathy. Am J Ophthalmol2000; 130: 187–191.
42.
ChanWMLamDSLaiTY, et al. Treatment of choroidal neovascularization in central serous chorioretinopathy by photodynamic therapy with verteporfin. Am J Ophthalmol2003; 136: 836–845.
43.
MudvariSSGoffMJFuAD, et al. The natural history of pigment epithelial detachment associated with central serous chorioretinopathy. Retina2007; 27: 1168–1173.
44.
KaracorluMErsozMGArfS, et al. Long-term follow-up of pachychoroid pigment epitheliopathy and lesion characteristics. Graefes Arch Clin Exp Ophthalmol2018; 256: 2319–2326.
45.
GhadialiQDansinganiKKFreundKB. Focal choroidal excavation and choroidal neovascularization with associated pachychoroid. Retin Cases Brief Rep2016; 10: 293–296.
46.
KovacsKDGonzalezLAWeissSJ, et al. Focal choroidal excavation expansion following treatment of associated choroidal neovascular membrane. Ophthalmic Surg Lasers Imaging Retina2019; 51: 54–57.
47.
ShahRCGopalakrishnanMGoyalA, et al. Focal choroidal excavation: cause or effect?Indian J Ophthalmol2019; 67: 696–698.
48.
Zheng-yuCLeiSWen-binW. Morphological changes of focal choroidal excavation. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol2019; 257: 2111–2117.
49.
HoACYannuzziLAPisicanoK, et al. The natural history of idiopathic subfoveal choroidal neovascularization. Ophthalmology1995; 102: 782–789.
50.
KimHLeeKLeeCS, et al. Subfoveal choroidal thickness in idiopathic choroidal neovascularization and treatment outcomes after intravitreal bevacizumab therapy. Retina2015; 35: 481–486.
51.
CaoXSPengXYYouQS, et al. Choroidal thickness in idiopathic subfoveal choroidal neovascularization. Ophthalmologica2014; 231: 221–225.
52.
CaoXSPengXYYouQS, et al. Subfoveal choroidal thickness change after intravitreal ranibizumab for idiopathic choroidal neovascularization. Retina2014; 34: 1554–1559.
53.
AhnSJKimTWAhnJ, et al. Subfoveal choroidal thickness in idiopathic choroidal neovascularization. Ophthalmology2014; 121: 1486–1487.e2.
54.
LeeMLeeHKimHC, et al. Changes in stromal and luminal areas of the choroid in pachychoroid diseases: insights into the pathophysiology of pachychoroid diseases. Investig Ophthalmol Vis Sci2018; 59: 4896–4908.
55.
SpaideRFJaffeGJSarrafD. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group. Ophthalmology2020; 127: 616–636.
56.
HataMYamashiroKOotoS, et al. Intraocular vascular endothelial growth factor levels in pachychoroid neovasculopathy and neovascular age-related macular degeneration. Investig Ophthalmol Vis Sci2017; 58: 292–298.
57.
TeraoNKoizumiHKojimaK, et al. Distinct aqueous humour cytokine profiles of patients with pachychoroid neovasculopathy and neovascular age-related macular degeneration. Sci Rep2018; 8: 10520.
58.
KnickelbeinJEChanCCSenHN, et al. Inflammatory mechanisms of age-related macular degeneration. Int Ophthalmol Clin2015; 55: 63–78.
59.
ParmeggianiFRomanoMRCostagliolaC, et al. Mechanism of inflammation in age-related macular degeneration. Mediators Inflamm2012; 2012: 546786.
60.
HosodaYMiyakeMSchellevisRL, et al. Genome-wide association analyses identify two susceptibility loci for pachychoroid disease central serous chorioretinopathy. Commun Biol2019; 2: 468.
61.
HosodaYYoshikawaMMiyakeM, et al. CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy. Proc Natl Acad Sci U S A2018; 115: 6261–6266.
62.
AzumaKTanXAsanoS, et al. The association of choroidal structure and its response to anti-VEGF treatment with the short-time outcome in pachychoroid neovasculopathy. PLoS One2019; 14: e0212055.
63.
TsaiDCChenSJHuangCC, et al. Epidemiology of idiopathic central serous chorioretinopathy in Taiwan, 2001–2006: a population-based study. PLoS One2013; 8: e66858.
64.
YinHFangXMaJ, et al. Idiopathic choroidal neovascularization: intraocular inflammatory cytokines and the effect of intravitreal ranibizumab treatment. Sci Rep2016; 6: 31880.
65.
AnantharamanGShethJBhendeM, et al. Polypoidal choroidal vasculopathy: pearls in diagnosis and management. Indian J Ophthalmol2018; 66: 896–908.
66.
RosenfeldPJBrownDMHeierJS, et al. Ranibizumab for neovascular age-related macular degeneration. New Engl J Med2006; 355: 1419–1431.
67.
LarsenMSchmidt-ErfurthULanzettaP, et al. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results. Ophthalmology2012; 119: 992–1000.
68.
AttanasioMMaggioEArenaF, et al. Swept source optical coherence tomography angiography findings in a case of pachychoroid neovasculopathy in retinitis pigmentosa. Retin Cases Brief Rep. Epub ahead of print 6 January 2020. DOI: 10.1097/icb.0000000000000962.
69.
VukojevićNSikićJKatusićD, et al. Types of central serous retinopathy, analysis of shape, topographic distribution and number of leakage sites. Coll Antropol2001; 25(Suppl): 83–87.
70.
GassJDM. Stereoscopic atlas of macular diseases. 3rd ed.St Louis: C V Mosby, 1987, p.12.
71.
Macular Photocoagulation Study Group. Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Macular Photocoagulation Study Group. Arch Ophthalmol1991; 109: 1242–1257.
72.
Macular Photocoagulation Study Group. Occult choroidal neovascularization: influence on visual outcome in patients with age-related macular degeneration. Arch Ophthalmol1996; 114: 400–412.
73.
DestroMPuliafitoCA. Indocyanine green videoangiography of choroidal neovascularization. Ophthalmology1989; 96(6): 846–853.
74.
YannuzziLASlakterJSSorensonJA, et al. Digital indocyanine green videoangiography and choroidal neovascularization. Retina1992; 12: 191–223.
75.
GuyerDRYannuzziLASlakterJS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch Ophthalmol1994; 112: 1057–1062.
76.
Gajdzik-GajdeckaUDoreckaMNitaE, et al. Indocyanine green angiography in chronic central serous chorioretinopathy. Med Sci Monit2012; 18: CR51–CR57.
77.
YangLJonasJBWeiW. Optical coherence tomography-assisted enhanced depth imaging of central serous chorioretinopathy. Investig Ophthalmol Vis Sci2013; 54: 4659–4665.
78.
St.MartinJMRodmanJPizzimentiJJ, et al. The “double-layer sign”: in vivo imaging of polypoidal choroidal vasculopathy. Optom Vis Sci2013; 90: e293–e300.
79.
SatoTKishiSWatanabeG, et al. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina2007; 27: 589–594.
80.
ShethJAnantharamanGChandraS, et al. “Double-layer sign” on spectral domain optical coherence tomography in pachychoroid spectrum disease. Indian J Ophthalmol2018; 66: 1796–1801.
81.
WaldsteinSMFaatzHSzimacsekM, et al. Comparison of penetration depth in choroidal imaging using swept source vs spectral domain optical coherence tomography. Eye (Lond)2015; 29: 409–415.
82.
SrinivasanVJAdlerDCChenY, et al. Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head. Investig Ophthalmol Vis Sci2008; 49: 5103–5110.
83.
IovinoCPellegriniMBernabeiF, et al. Choroidal vascularity index: an in-depth analysis of this novel optical coherence tomography parameter. J Clin Med2020; 9: 595.
84.
AgrawalRGuptaPTanKA, et al. Choroidal vascularity index as a measure of vascular status of the choroid: measurements in healthy eyes from a population-based study. Sci Rep2016; 6: 21090.
85.
YeoJHOhRKimYJ, et al. Choroidal neovascularization secondary to central serous chorioretinopathy: OCT angiography findings and risk factors. JOJ Ophthalmol2020; 2020: 7217906.
86.
KohALeeWKChenLJ, et al. EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina2012; 32: 1453–1464.
87.
HageRMrejenSKrivosicV, et al. Flat irregular retinal pigment epithelium detachments in chronic central serous chorioretinopathy and choroidal neovascularization. Am J Ophthalmol2015; 159: 890–903.e3.
88.
AgarwalAAggarwalKGuptaV. Management of neovascular age-related macular degeneration: a review on landmark randomized controlled trials. Middle East Afr J Ophthalmol2016; 23: 27–37.
89.
LaiTYYStaurenghiGLanzettaP, et al. Efficacy and safety of ranibizumab for the treatment of choroidal neovascularization due to uncommon cause: twelve-month results of the MINERVA study. Retina2018; 38: 1464–1477.
90.
Padrón-PérezNAriasLRubioM, et al. Changes in choroidal thickness after intravitreal injection of anti-vascular endothelial growth factor in pachychoroid neovasculopathy. Investig Ophthalmol Vis Sci2018; 59: 1119–1124.
91.
HataMOishiATsujikawaA, et al. Efficacy of intravitreal injection of aflibercept in neovascular age-related macular degeneration with or without choroidal vascular hyperpermeability. Investig Ophthalmol Vis Sci2014; 55: 7874–7880.
92.
ChoHJJungSHChoS, et al. Intravitreal anti-vascular endothelial growth factor treatment for pachychoroid neovasculopathy. J Ocul Pharmacol Ther2019; 35: 174–181.
93.
SchwormBLuftNKeidelLF, et al. Response of neovascular central serous chorioretinopathy to an extended upload of anti-VEGF agents. Graefes Arch Clin Exp Ophthalmol2020; 258: 1013–1021.
94.
TeraoNKoizumiHKojimaK, et al. Association of upregulated angiogenic cytokines with choroidal abnormalities in chronic central serous chorioretinopathy. Investig Ophthalmol Vis Sci2018; 59: 5924–5931.
95.
KoizumiHYamagishiTYamazakiT, et al. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol2013; 155(2): 305–313.e1.
96.
LeeJHLeeWK. One-year results of adjunctive photodynamic therapy for Type 1 neovascularization associated with thickened choroid. Retina2016; 36: 889–895.
97.
RoyRSaurabhKShahD, et al. Treatment outcomes of pachychoroid neovasculopathy with photodynamic therapy and anti-vascular endothelial growth factor. Indian J Ophthalmol2019; 67: 1678–1683.
98.
MarukoIIidaTSuganoY, et al. Subfoveal retinal and choroidal thickness after verteporfin photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol2011; 151: 594–603.e1.
99.
SchwormBLuftNKeidelLF, et al. Ranibizumab non-response in pachychoroid neovasculopathy: effects of switching to aflibercept. Sci Rep2020; 10: 8439.
100.
GharbiyaMCrucianiFMariottiC, et al. Choroidal thickness changes after intravitreal antivascular endothelial growth factor therapy for age-related macular degeneration: ranibizumab versus aflibercept. J Ocul Pharmacol Ther2015; 31: 357–362.
101.
MatsumotoHMukaiRKikuchiY, et al. One-year outcomes of half-fluence photodynamic therapy combined with intravitreal injection of aflibercept for pachychoroid neovasculopathy without polypoidal lesions. Jpn J Ophthalmol2020; 64: 203–209.
102.
KitajimaYMaruyama-InoueMItoA, et al. One-year outcome of combination therapy with intravitreal anti-vascular endothelial growth factor and photodynamic therapy in patients with pachychoroid neovasculopathy. Graefes Arch Clin Exp Ophthalmol2020; 258: 1279–1285.
103.
ChhablaniJKozakIPichiF, et al. Outcomes of treatment of choroidal neovascularization associated with central serous chorioretinopathy with intravitreal antiangiogenic agents. Retina2015; 35: 2489–2497.
104.
SacconiRTomassoLCorbelliE, et al. Early response to the treatment of choroidal neovascularization complicating central serous chorioretinopathy: a OCT-angiography study. Eye2019; 33: 1809–1817.
105.
KohALaiTYYTakahashiK, et al. Efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy: a randomized clinical trial. JAMA Ophthalmol2017; 135: 1206–1213.
106.
GomiFOshimaYMoriR, et al. Initial versus delayed photodynamic therapy in combination with ranibizumab for treatment of polypoidal choroidal vasculopathy: the Fujisan study. Retina2015; 35: 1569–1576.
107.
LeeWKIidaTOguraY, et al. Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy in the PLANET study: a randomized clinical trial. JAMA Ophthalmol2018; 136: 786–793.
